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Review
. 2011 Nov;22(11):443-9.
doi: 10.1016/j.tem.2011.07.001. Epub 2011 Aug 18.

Regulation of Gonadotropin-Releasing Hormone Neurons by Glucose

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Free PMC article
Review

Regulation of Gonadotropin-Releasing Hormone Neurons by Glucose

Alison V Roland et al. Trends Endocrinol Metab. .
Free PMC article

Abstract

Reproduction is influenced by energy balance, but the physiological pathways mediating their relationship have not been fully elucidated. As the central regulators of fertility, gonadotropin-releasing hormone (GnRH) neurons integrate numerous physiological signals, including metabolic cues. Circulating glucose levels regulate GnRH release and might in part mediate the effects of negative energy balance on fertility. Existing evidence suggests that neural pathways originating in the hindbrain, as well as in the hypothalamic feeding nuclei, transmit information concerning glucose availability to GnRH neurons. Here we review recent evidence suggesting that GnRH neurons might directly sense changes in glucose availability by a mechanism involving AMP-activated protein kinase. These findings expand our understanding of how metabolic signaling in the brain regulates reproduction.

Figures

Figure 1
Figure 1
GnRH neurons are inhibited by both low glucose and AICAR. (a). Plot of firing rate (binned in 60-second intervals) of a GnRH neuron from an ovariectomized mouse in response to a reduction from 4.5 mM to 0.2 mM glucose. Shaded region indicates time of low glucose exposure. Low glucose slowly inhibits the firing rate; this effect is not immediately reversed upon restoration of 4.5 mM glucose. The decrease at the return to high glucose in this example was typical of many GnRH neurons; this observation was found to be a coincidental aspect of the temporal nature of the response to low glucose, rather than a further suppression by restoration to normal glucose. (b). AICAR, which activates AMPK, inhibits GnRH neuron firing in 4.5 mM glucose. (c, d). Whole-cell, current-clamp recordings demonstrating low glucose (c) and AICAR (d) suppression of GnRH neuron action potential firing rate. mV, millivolts. Adapted from reference with permission.
Figure 2
Figure 2
Putative sites of glucose action in the brain to regulate GnRH neuronal function. Glucose may act on distal brain regions in the hindbrain area postrema (AP), and in the arcuate (ARC) and lateral hypothalamus (LHA), which project (both directly and indirectly) to GnRH neurons. In addition, glucose may alter the function of GnRH neurons through direct action mediated by AMPK, or through effects on proximal glial cells.

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